To be effective as therapeutic agents, centrally acting pharmaceuticals must cross the blood-brain barrier (BBB). Conversely, to be devoid of unwanted central nervous system (CNS) effects, peripherally acting pharmaceuticals should demonstrate limited ability to cross the BBB. In either case, the BBB permeability of a pharmaceutical candidate needs to be known. However, the experimental determination of blood-brain partitioning is difficult, time-consuming, costly and unsuitable for screening large collections of chemicals. A broadly applicable method for predicting the BBB permeation of pharmaceutical candidates at an early stage of discovery would have a significant impact in pharmaceutical research and development. Methods which produce reliably predictable data related to BBB permeation for large numbers of compounds at an early stage of the discovery/development process are urgently needed.
Therefore, it is an object of this invention to provide a robust, efficient and predictive method for the in vitro determination of the BBB permeation capabilities of a test compound such as a potential pharmaceutical agent.
It is another object of this invention to provide a membrane composition useful for the in vitro determination of the BBB permeation capabilities of a test compound.
It is a feature of this invention that the BBB permeation determinative method and composition provide high predictive value and high throughput efficiency.
It is another feature of this invention that said method and composition are adaptable to standard laboratory robotics platforms.
These and other objects and features of the invention will become more apparent by the detailed description set forth hereinbelow.